Blockage of transient receptor potential vanilloid 4 alleviates myocardial ischemia/reperfusion injury in mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Qian Dong, Jing Li, Qiong-Feng Wu, Ning Zhao, Cheng Qian, Dan Ding, Bin-Bin Wang, Lei Chen, Ke-Fang Guo, Dehao Fu, Bing Han, Yu-Hua Liao, Yi-Mei Du

ABSTRACT

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24-72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion. Importantly, the therapeutic window for HC-067047 lasts for at least 12 h following reperfusion. Furthermore, treatment with HC-067047 reduced apoptosis, as evidenced by the decrease in TUNEL-positive myocytes, Bax/Bcl-2 ratio, and caspase-3 activation. Meanwhile, treatment with HC-067047 attenuated the decrease in the activation of reperfusion injury salvage kinase (RISK) pathway (phosphorylation of Akt, ERK1/2, and GSK-3β), while the activation of survival activating factor enhancement (SAFE) pathway (phosphorylation of STAT3) remained unchanged. In addition, the anti-apoptotic effects of HC-067047 were abolished by the RISK pathway inhibitors. We conclude that blockade of TRPV4 reduces apoptosis via the activation of RISK pathway, and therefore might be a promising strategy to prevent myocardial I/R injury. More... »

PAGES

42678

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep42678

DOI

http://dx.doi.org/10.1038/srep42678

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1083843214

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28205608


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